1. Field of the Invention
This invention relates to compositions and methods for increasing the rate of healing of tissue wounds in animals using cationic steroid antimicrobials (CSAs).
2. Relevant Technology
Wound healing is the complex and dynamic process of self-repair to restore cellular structures and tissue layers after an injury has occurred. The human wound healing process is divided into three distinct phases: the inflammatory phase, the proliferative phase, and the remodeling phase. The wound healing process may be further broken down beyond the three broad phases to a complex and coordinated series of biochemical events that include chemotaxis, phagocytosis, neocollagenesis, collagen degradation, and collagen remodeling to repair the damage. In addition, angiogenesis, epithelization, and the production of new glycosaminoglycans (GAGs) and proteoglycans are vital to the wound healing process. The culmination of these biological processes results in the replacement of normal skin structures with fibroblastic mediated scar tissue.
Prior to the initiation of the inflammatory phase, the clotting cascade begins to stop blood loss via clotting. Once clotting has begun, various soluble factors, including chemokines and cytokines, are released to attract cells to the site of injury. Growth factors, which are cytokines released by platelets, stimulate cells to accelerate their rate of division leading to increased healing rates. Platelets also release other proinflammatory factors like serotonin, bradykinin, prostaglandins, prostacyclins, thromboxane, and histamine, which serve a number of purposes, including to increase cell proliferation and migration to the area and to cause blood vessels to become dilated and porous.
The inflammation phase can be further broken down into four biochemical processes. First, immediately after a blood vessel is breached, ruptured cell membranes release inflammatory factors like thromboxanes and prostaglandins that result in vasoconstriction to prevent blood loss and to collect inflammatory cells and factors. Second, polymorphonuclear neutrophils (PMNs) arrive at the wound site, phagocytose debris and bacteria. Neutrophils also cleanse the wound by secreting proteases that break down damaged tissue. Third, neutrophils cleanse the injured area via the phagocytosis of debris, bacteria, neutrophils, damaged cells and tissue, and any other foreign cells or material. Macrophages also secrete a number of factors that push wound healing toward the next phase. Finally, inflammation dies down, fewer inflammatory factors are secreted, existing ones are broken down, and numbers of neutrophils and macrophages are reduced at the wound site.
The proliferative phase begins with the arrival of fibroblasts at the wound site, marking the onset of the proliferative phase, which biologically begins with angiogenesis. Angiogenesis or neovascularization is the process which occurs concurrently with fibroblast proliferation when endothelial cells migrate to the area of the wound. Fibroplasia and granulation begin during angiogenesis as a result of fibroblast recruitment and extracellular matrix formation. Then collagen and fibronectin are deposited by the fibroblast at the site of tissue granulation. Once collagen deposition has occurred, epithelialization takes place as a result of the presence of keratinocytes arriving at the newly deposited extracellular matrix. The final step in the proliferative phase is contraction, which requires the presence of neomyoblasts to connect the scar tissue to the surrounding healthy tissue and to pull the edges of the scar tissue together, restoring tensile strength to the skin surrounding the previously injured area.
A need exists to develop compositions and methods to enhance wound healing.